Migraine attacks are characterized by moderate to severe ain, nausea, vomiting, increased sensitivity to lights, sounds and odors, and cutaneous allodynia. Migraine, which afflicts 36 million Americans, causes substantial individual and societal burden. Although individual migraine attacks last for several hours to a few days, there is often persistence of hypersensitivities such as photophobia, phonophobia and osmophobia and cutaneous sensitization between migraine attacks. Furthermore, migraine attacks can be triggered by light, noise and odors. The mechanisms for interictal persistence of these symptoms and the mechanisms by which environmental stimuli trigger migraine attacks are unknown. In this set of experiments we address these associations by using functional magnetic resonance imaging to investigate functional networks in episodic and chronic migraine subjects. The specific aims will test the following hypotheses: 1) stimulus-induced deactivation of the default mode network is less in migraine subjects compared to non-migraine controls; 2) migraineurs have stronger functional connectivity among regions of the brain responsible for pain processing and between these pain processing regions and those responsible for processing of auditory, visual and olfactory stimuli; 3) abnormal default mode network deactivation and stronger functional connectivity among pain regions and between pain regions and regions of the auditory, visual and olfactory networks are positively associated with greater migraine burden. It is necessary to establish and assess functional networks in migraine so that future studies can investigate methods to normalize potentially aberrant networks and block activation of these networks, actions that may prevent and alleviate migraine symptoms. The candidate is an Assistant Professor of Neurology and Anesthesiology and Director of the Washington University Headache Center in St. Louis, Missouri. The candidate's short-term goal is to enhance his functional neuroimaging skills so that he can transition from mentored to independent patient-oriented research employing functional imaging to investigate the pain and associated symptoms (hypersensitivities to and triggering of migraine by sound, light and odors and cutaneous sensitization) of migraine. Once the relationships between migraine headache and these associated symptoms are described, the longer-term goal is to explore mechanisms by which to normalize these relationships or block activation of functional networks that lead to migraine symptoms. The multidisciplinary team of world-class mentors and the extensive intellectual and physical resources available at Washington University will optimize the candidate's training experience and likelihood for successful transition to independent research. PUBLIC HEALTH RELEVANCE: Migraine is an exceedingly common disease, affecting 12% of the population. Migraine results in substantial disability due to headache pain, hypersensitivities to environmental stimuli, and skin sensitization. Unfortunately, migraine is poorly understood and can be difficult to treat. This study will employ advanced neuroimaging techniques to investigate functional networks in the brain that may explain the relationship between migraine headache and hypersensitivities, as well as how environmental stimuli trigger a migraine attack. Description of these functional networks will allow for future investigations into methods to normalize or block activation of these networks, methods that may reduce migraine symptoms and improve the lives of millions of migraine sufferers.